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Protection of the Small Intestinal Clonogenic Stem Cells from Radiation-Induced Damage by Pretreatment with Interleukin 11 also Increases Murine Survival Time

CRC Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, United Kingdom

Key Words. Intestinal stem cells • Clonogenic cells • Radiation • 5-Fluorouracil • Survival time

Dr. C.S. Potten, CRC Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 9BX, United Kingdom.

The effect of administering recombinant human interleukin 11 in conjunction with cytotoxic insults to the gastrointestinal tract has been studied using the crypt microcolony assay for stem cell function and whole-animal survival time studies. The cytotoxic regimens include single doses of rays; single doses of 5-fluorouracil (5-FU) and multiple doses of 5-FU spaced 6 h apart. Interleukin 11 (IL-11) (100 µg/kg) delivered over a period of time prior to cytotoxic exposure afforded protection to the clonogenic cells in the crypts as seen with the microcolony assay and prolonged the animal survival time following radiation exposure. Continuing this dose of IL-11 after cytotoxic exposure afforded little additional protection.

Three doses of 5-FU 6 h apart generated crypt survival curves similar to those obtained after a single dose of rays. IL-11 given prior to two doses of 5-FU effectively abolished the cytotoxic effect of the second dose of 5-FU; i.e., 2.5-3.0 times more crypts survived if IL-11 was administered when the higher 5-FU doses are considered. IL-11 given before a dose of 12 Gy of rays prolonged the survival time of animals by three to four days. This confirms earlier studies demonstrating that protecting clonogenic cells in the crypt survival assay can result in beneficial effects on whole-animal survival times.

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